Omapatrilat (I) is a potent inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo: ##STR2##
Omapatrilat was developed at the Bristol-Myers Squibb Pharmaceutical Research Institute as the first of a new class of compounds capable of simultaneously inhibiting ACE and NEP and is currently undergoing large scale clinical trials as an anti-hypertensive. See Omapatrilat. Drugs R D 1999 Apr;1(4):350-1.
Currently, omapatrilat is synthesized using (S)-hydroxy amino acid (II) as one of the key starting materials: ##STR3##
The hydroxyl group of compound (II) must be converted to an aldehyde as a prerequisite step in the synthesis os compound (I), omapatrilat. This oxidation to an aldehyde currently requires several steps and/or noxious reagents. See Robl, J. A., et al. J. Med. Chem. 1997, 40, 1570-1577; Robl, J. A., et al. J. Med. Chem. 1996, 39, 494-502.
It is therefore desirable to find alternatives to compound (II) that reduce the number of requisite synthetic steps and eliminate the use of noxious reagents. It is further desirable to develop a pathway suitable for the production of such intermediates.